Microarrays of biochemical substances have been used extensively for biological analysis as is well known in the art. The ability to manufacture microarrays in an efficient and cost-effective manner is of considerable interest to researchers worldwide and of significant commercial value. Various types of microarray manufacturing devices and technologies have been described previously. Each of these approaches has certain deficiencies that are addressed by the present invention.
Combinatorial array approaches, such as described by Southern et al. (U.S. Pat. Nos. 5,770,367, 5,700,637, and 5,436,327), Pirrung et al. (U.S. Pat. No. 5,143,854), Fodor et al. (U.S. Pat. Nos. 5,744,305 and 5,800,992), and Winkler et al. (U.S. Pat. No. 5,384,261), have been used with success in cases in which polymers of short sequences are required. The combinatorial approaches generate significant biological and chemical diversity but are unable to construct microarrays of large macromolecules. The combinatorial technologies can also be expensive and difficult to implement.
Ink-jetting and other "drop-on-demand" devices also permit the fabrication of biological and chemical arrays as shown by Brennan (U.S. Pat. No. 5,474,796), Tisone (U.S. Pat. No. 5,741,554), and Hayes et al. (U.S. Pat. No. 5,658,802). These non-contact technologies are deficient due to their inability to array large numbers of samples easily and to control the quality of the resultant microarrays.
A third category of arraying devices work by direct surface contact printing as described by Augenlicht (U.S. Pat. No. 4,981,783), Drmanac et al. (U.S. Pat. No. 5,525,464), Roach et al. (U.S. Pat. No. 5,770,151), and Brown et al. (U.S. Pat. No. 5,807,522). Each of these technologies has been successful but is less robust than the device of the present invention. Deficiencies of the earlier technologies include imprecise sample uptake and delivery as well as lack of durability.
The present invention describes a novel device that allows the rapid and cost-effective manufacture of microarrays of biochemical substances. The device is made with advanced machining technologies such as an electronic discharge machine (EDM), thereby providing for precise sample uptake and delivery. The device is suitable for use in a basic research or a commercial production environment and can be attached to a motion control system that allows precise three-dimensional movements.